ANALYSIS OF MICROTUBULE-ASSOCIATED PROTEIN-TAU GLYCATION IN PAIRED HELICAL FILAMENTS

Alzheimer's disease is typified by the characteristic histopathologica l lesions of neurofibrillar plaques and tangles. The latter are compos ed of paired helical filaments (PHFs), the major components of which a re modified forms of the microtubule-associated protein tau. The exact nature of these modifications remains unknown, although the presence of hyperphosphorylated tau in PHFs argues strongly that phosphorylatio n is one of the modifications that result in the polymerization of tau into PHFs. However, hyperphosphorylation alone is insufficient to exp lain the formation of PHFs. In an attempt to characterize other post-t ranslational modifications of PHF-tau, we have analyzed its glycation. A fraction of PHF tau seems to be glycated in. vivo, whereas soluble tau from either Alzheimer's disease or non-demented human brain is not glycated at all. Purified tau from bovine brain can be efficiently gl ycated in vitro. Tau glycation is accompanied by a decrease in the tau binding to tubulin. These results support the view that glycation may be one of the modifications hampering the binding of tan to tubulin i n Alzheimer's disease, thus facilitating tau aggregation into PHFs.